Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth

Pediatrics. 2003 Nov;112(5):1016-20. doi: 10.1542/peds.112.5.1016.


Objective: Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, we hypothesized that prolonged low IGF-I in premature infants might be a risk factor for ROP.

Design: We conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages: 24-32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC).

Results: Low serum IGF-I values correlated with later development of ROP. The mean IGF-I +/- SEM level during postmenstrual ages 30-33 weeks was lowest with severe ROP (25 +/- 2.41 micro g/L), 29 +/- 1.76 micro g/L with moderate ROP, and 33 +/- 1.72 micro g/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached >33 micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and 52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP, BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41-3.43) if IGF-I was <or=33 micro g/L at 33 weeks' postmenstrual age.

Conclusions: These results indicate that persistent low serum concentrations of IGF-I after premature birth are associated with later development of ROP and other complications of prematurity. IGF-I is at least as strong a determinant of risk for ROP as postmenstrual age at birth and birth weight.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Birth Weight
  • Bronchopulmonary Dysplasia / blood
  • Bronchopulmonary Dysplasia / epidemiology
  • Cerebral Hemorrhage / blood
  • Cerebral Hemorrhage / epidemiology
  • Enterocolitis, Necrotizing / blood
  • Enterocolitis, Necrotizing / epidemiology
  • Fetal Growth Retardation / blood
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature / blood*
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / deficiency*
  • Longitudinal Studies
  • Prospective Studies
  • Retinopathy of Prematurity / blood*
  • Retinopathy of Prematurity / epidemiology
  • Risk Factors
  • Severity of Illness Index
  • Sweden / epidemiology


  • Insulin-Like Growth Factor I